During development axons undergo long-distance migrations as instructed by guidance molecules and their receptors, such as UNC-6/Netrin and UNC-40/DCC. Guidance cues act through long-range diffusive gradients (chemotaxis) or local adhesion (haptotaxis). However, how these discrete modes of action guide axons in vivo is poorly understood. Using time-lapse imaging of axon guidance in C. elegans, we demonstrate that UNC-6 and UNC-40 are required for local adhesion to an intermediate target and subsequent directional growth. Exogenous membrane-tethered UNC-6 is sufficient to mediate adhesion but not directional growth, demonstrating the separability of haptotaxis and chemotaxis. This conclusion is further supported by the endogenous UNC-6 distribution along the axon’s route. The intermediate and final targets are enriched in UNC-6 and separated by a ventrodorsal UNC-6 gradient. Continuous growth through the gradient requires UNC-40, which recruits UNC-6 to the growth cone tip. Overall, these data suggest that UNC-6 stimulates stepwise haptotaxis and chemotaxis in vivo.

Brain states fluctuate between exploratory and consummatory phases of behavior. These state changes affect both internal computation and the organism’s responses to sensory inputs. Understanding neuronal mechanisms supporting exploratory and consummatory states and their switching requires experimental control of behavioral shifts and collecting sufficient amounts of brain data. To achieve this goal, we developed the ThermoMaze, which exploits the animal’s natural warmth-seeking homeostatic behavior. By decreasing the floor temperature and selectively heating unmarked areas, we observed that mice avoided the aversive state by exploring the maze and finding the warm spot. In its design, the ThermoMaze is analogous to the widely used water maze but without the inconvenience of a wet environment and, therefore, allows the collection of physiological data in many trials. We combined the ThermoMaze with electrophysiology recording, and report that spiking activity of hippocampal CA1 neurons during sharp-wave ripple events encode the position of mice. Thus, place-specific firing is not confined to locomotion and associated theta oscillations but persist during waking immobility and sleep at the same location. The ThermoMaze will allow for detailed studies of brain correlates of immobility, preparatory–consummatory transitions, and open new options for studying behavior-mediated temperature homeostasis.